KCNQ1 Variant N593S

Summary of observed carriers, functional annotations, and structural context for KCNQ1 N593S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

35%

3/11 effective observations

Total carriers

1

0 LQT1 · 1 unaffected

Functional studies

0

Publications with functional data

N593S is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 3 individuals with LQT1 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.4 0.392 0 0.518 42

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. BLAST-PSSM reflects evolutionary conservation; more negative values indicate rarer substitutions. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT1 Other Disease
Literature, cohort, and gnomAD – 1 1 0 –
Variant features alone – 15 7 3 –

Totals may differ from individual publications due to duplicate patients removed during curation.

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near N593S.
Neighbour residue Distance (Å) Observed variants
593 0 N593S,
592 4
594 4 R594Q, R594P,
591 5 R591H, R591C, R591L,
595 5 V595L, V595L
590 7 A590T,
596 7 E596del, E596K,
589 8 G589D, G589S,
597 8
588 8 I588F,
598 8 K598R,
587 9 T587M, T587R,
599 9
586 10 N586D,
600 10 T600M,
585 11 S585N,
601 11
584 11 G584S,
602 11
583 12 R583H, R583C, R583G,
603 12
582 13
604 13
581 13
605 13
580 14 S580G, S580N,
606 14
579 14
607 14 A607T,
578 15 E578K, E578V,
608 15